Evolution of BK virus based on complete genome data.

The human polyomavirus BK virus (BKV) is ubiquitous in humans, infecting children asymptomatically. BKV is the only primate polyomavirus that has subtypes (I-IV) distinguishable by immunological reactivity. Nucleotide (nt) variations in a major capsid protein (VP1) gene region (designated the epitope region), probably responsible for antigenic diversity, have been used to classify BKV isolates into subtypes. Here, with all the protein-encoding gene sequences, we attempted to elucidate the evolutionary relationships among 28 BKV isolates belonging to subtypes I, III, and IV (no isolate belonging to subtype II, a minor one, was included). First, using the GTR + Gamma + I model, maximum likelihood trees were reconstructed for individual viral genes as well as for concatenated viral genes. On the resultant trees, the 28 BKV isolates were consistently divided into three clades corresponding to subtypes I, III, and IV, although bootstrap probabilities are not always high. Then we used more sophisticated likelihood models, one of which takes account of codon structure, to elucidate the phylogenetic relationships among BKV subtypes, but the phylogeny of the deep branchings remained ambiguous. Furthermore, the possibility of positive selection in the evolution of BKV was examined using the nonsynonymous/synonymous rate ratio as a measure of selection. An analysis based on entire genes could not detect any strong evidence for positive selection, but that based on the epitope region identified a few sites potentially under positive selection (these sites were among those showing subtype linked polymorphisms).